Hemodialysis-related induction of beta-2-microglobulin and interleukin-1 synthesis and release by mononuclear phagocytes

Nephron
P J KnudsenK M Koch

Abstract

We have investigated beta 2-microglobulin (beta 2M) synthesis and release by blood leukocytes and isolated mononuclear phagocytes. Recent interest in beta 2M has developed since the discovery that this protein forms amyloid fibrils in patients undergoing long-term, chronic hemodialysis and that these patients have greatly elevated levels of monomeric beta 2M in their circulation. Since hemodialysis-related factors that increase beta 2M production are unknown, we evaluated beta 2M production by freshly prepared leukocytes and monocyte-derived macrophages under a variety of conditions. We utilized a novel enzyme-linked immunoabsorbant assay to quantitate beta 2M concentrations, and monitored interleukin-1 and beta 2M synthesis by immunoprecipitation. Incubation of leukocytes with Cuprophan or Hemophan does not increase beta 2M release. Adherence of macrophages onto polystyrene or Cuprophan membranes induces neither interleukin-1 nor beta 2M synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin-1 induces synthesis and release of beta 2 M, indicating that beta 2 M synthesis is increased during macrophage activation. Exposing leukocytes or macro...Continue Reading

Citations

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